HER2/Neu Conversion Rates Make Retesting Essential in GYN Cancers

Susana M. Campos, MD, MPH, clinical director of the Division of Gynecologic Oncology and director of Educational Initiatives at Dana-Farber Cancer Institute, and assistant professor of medicine at Harvard Medical School, explained why retesting HER2/neu status at recurrence is critical in gynecologic cancers, even when the primary tumor was immunohistochemistry (IHC) 0 or 1+.

As part of a Satellite Sessions post-program conversation, Campos discussed how frequently HER2/neu expression can convert between primary and recurrent disease across ovarian, endometrial, and cervical cancers, and why this tumor heterogeneity mattered clinically. A shift to IHC 3+ at recurrence can open the door to HER2-directed antibody-drug conjugates (ADCs) such as trastuzumab deruxtecan (T-DXd; Enhertu), which has shown activity in HER2-expressing gynecologic (GYN) cancers in the phase 2 DESTINY-PanTumor02 trial (NCT04482309).

Transcript:

CancerNetwork: The panel universally agreed on retesting HER2 status at recurrence, even if the primary tumor was IHC 0 or 1+. How often do you catch a shift to IHC 3 or higher at recurrence, and how does that change your approach?

Campos: It’s a great question and very pertinent to our clinical practice. This centers on HER2/neu conversion, and in truth, the data [are] limited in gynecological malignancies when compared with that of breast cancer. From the literature we do have, in ovarian cancer, you can get a conversion in about 35% to 60%, depending on the study you read. In endometrial cancer, there’s tremendous intratumoral heterogeneity, up to 55%, and this is also the case in cervical cancer, where there’s a high discordance rate between the biopsy and the hysterectomy.

The bottom line, although we don’t have exact numbers, is that HER2/neu expression in GYN cancer has marked tumor heterogeneity, so it’s incredibly important to retest these individuals. There are times when you might get a HER2/neu expression of 0 or 1+, making the patient not eligible for an ADC such as trastuzumab deruxtecan. If you biopsy another site, or analyze another site on the archived specimen, you can get a different answer, and that opens the door to a drug that is very active in gynecological malignancy. It’s very important to biopsy if deemed safe.

Reference

Lee JY, Oaknin A, Manso L, et al. Trastuzumab deruxtecan in HER2-expressing gynecologic cancers from DESTINY-PanTumor02: antitumor activity, safety, and exploratory biomarker analyses. J Gynecol Oncol. 2026;37(3):e65. doi:10.3802/jgo.2026.37.e65